The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
The insulin A-chain epitope recognized by human T cells is posttranslationally modified
Open accessAbstract
The autoimmune process that destroys the insulin-producing pancreatic β cells in type 1 diabetes (T1D) is targeted at insulin and its precursor, proinsulin. T cells that recognize the proximal A-chain of human insulin were identified recently in the pancreatic lymph nodes of subjects who had T1D. To investigate the specificity of proinsulin-specific T cells in T1D, we isolated human CD4+ T cell clones to proinsulin from the blood of a donor who had T1D. The clones recognized a naturally processed, HLA DR4–restricted epitope within the first 13 amino acids of the A-chain (A1–13) of human insulin. T cell recognition was dependent on the formation of a vicinal disulfide bond between adjacent cysteine residues at A6 and A7, which did not alter binding of the peptide to HLA DR4. CD4+ T cell clones that recognized this epitope were isolated from an HLA DR4+ child with autoantibodies to insulin, and therefore, at risk for T1D, but not from two healthy HLA DR4+ donors. We define for the first time a novel posttranslational modification that is required for T cell recognition of the insulin A-chain in T1D.
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Cites
Eisenbarth (1986) · doi:10.1056/nejm198605223142106 · Cited by 1,659
Pugliese, A., Zeller, M., Fernandez, A., Zalcberg, L. J., Bartlett, R. J., Ricordi, C., Pietropaolo, M., Eisenbarth, G. S., Bennett, S. T., & Patel, D. D. (1997) · Nature Genetics · doi:10.1038/ng0397-293 · Cited by 945
Insulin expression in human thymus is modulated by INS VNTR alleles at the IDDM2 locus
Vafiadis, P., Bennett, S. T., Todd, J. A., Nadeau, J., Grabs, R., Goodyer, C. G., Wickramasinghe, S., Colle, E., & Polychronakos, C. (1997) · Nature Genetics · doi:10.1038/ng0397-289 · Cited by 809 · cited 1×
“The T1D susceptibility locus IDDM2 maps to a variable number of tandem repeats (VNTRs) upstream of the insulin gene (7); the long class III VNTR allele is associated with higher levels of proinsulin mRNA in the thymus and decreased susceptibility to T1D (8, 9).”
BackgroundBennett, S. T., Lucassen, A. M., Gough, S. C. L., Powell, E. E., Undlien, D. E., Pritchard, L. E., Merriman, M. E., Kawaguchi, Y., Dronsfield, M. J., Pociot, F., et al. (1995) · Nature Genetics · doi:10.1038/ng0395-284 · Cited by 746
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Cited by
Dendrou, C. A., Petersen, J., Rossjohn, J., & Fugger, L. (2018) · Nature Reviews Immunology · doi:10.1038/nri.2017.143 · Cited by 787
Self-citationPathogenic CD4 T cells in type 1 diabetes recognize epitopes formed by peptide fusion
Delong, T., Wiles, T. A., Baker, R. L., Bradley, B., Barbour, G., Reisdorph, R., Armstrong, M., Powell, R. L., Reisdorph, N., Kumar, N., et al. (2016) · Science · doi:10.1126/science.aad2791 · Cited by 503
Self-citationScally, S. W., Petersen, J., Law, S. C., Dudek, N. L., Nel, H. J., Loh, K. L., Wijeyewickrema, L. C., Eckle, S. B. G., van Heemst, J., Pike, R. N., et al. (2013) · Journal of Experimental Medicine · doi:10.1084/jem.20131241 · Cited by 429
Self-citationBabon, J. A. B., DeNicola, M. E., Blodgett, D. M., Crèvecoeur, I., Buttrick, T. S., Maehr, R., Bottino, R., Naji, A., Kaddis, J., Elyaman, W., et al. (2016) · Nature Medicine · doi:10.1038/nm.4203 · Cited by 300
Recent advances in understanding type 1 diabetes
Christoffersson, G., Rodriguez-Calvo, T., & von Herrath, M. (2016) · F1000Research · doi:10.12688/f1000research.7356.1 · Cited by 32
Metadata
- Authors
- Mannering, S. I., Harrison, L. C., Williamson, N. A., Morris, J. S., Thearle, D. J., Jensen, K. P., Kay, T. W. H., Rossjohn, J., Falk, B. A., Nepom, G. T., & Purcell, A. W.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2005-10-31
- Volume
- 202
- Issue
- 9
- Pages
- 1191-1197
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2104663495
- Cited by
- 231
- References
- 5
- FWCI
- 3.87
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Mannering, S. I., Harrison, L. C., Williamson, N. A., Morris, J. S., Thearle, D. J., Jensen, K. P., Kay, T. W. H., Rossjohn, J., Falk, B. A., Nepom, G. T., & Purcell, A. W. (2005). The insulin A-chain epitope recognized by human T cells is posttranslationally modified. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20051251
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